Autism Research Centre, Department of Psychiatry, University of Cambridge, 18b Trumpington Road, Cambridge CB2 8AH, UK.
Mol Autism. 2014 Feb 18;5(1):14. doi: 10.1186/2040-2392-5-14.
Autism spectrum conditions (ASC) are a group of conditions characterized by difficulties in communication and social interaction, alongside unusually narrow interests and repetitive, stereotyped behaviour. Genetic association and expression studies have suggested an important role for the GABAergic circuits in ASC. Syntaxin 1A (STX1A) encodes a protein involved in regulation of serotonergic and GABAergic systems and its expression is altered in autism.
In this study, the association between three single nucleotide polymorphisms (SNPs) (rs4717806, rs941298 and rs6951030) in STX1A gene and Asperger syndrome (AS) were tested in 650 controls and 479 individuals with AS, all of Caucasian ancestry.
rs4717806 (P = 0.00334) and rs941298 (P = 0.01741) showed a significant association with AS, replicating previous results. Both SNPs putatively alter transcription factor binding sites both directly and through other variants in high linkage disequilibrium.
The current study confirms the role of STX1A as an important candidate gene in ASC. The exact molecular mechanisms through which STX1A contributes to the etiology remain to be elucidated.
自闭症谱系障碍(ASC)是一组以沟通和社交互动困难为特征的疾病,同时伴有异常狭窄的兴趣和重复、刻板的行为。遗传关联和表达研究表明 GABA 能回路在 ASC 中起着重要作用。突触融合蛋白 1A(STX1A)编码一种参与调节 5-羟色胺能和 GABA 能系统的蛋白质,其在自闭症中表达改变。
在这项研究中,测试了 STX1A 基因中的三个单核苷酸多态性(SNP)(rs4717806、rs941298 和 rs6951030)与阿斯伯格综合征(AS)之间的关联,共纳入 650 名对照者和 479 名白种人 AS 患者。
rs4717806(P=0.00334)和 rs941298(P=0.01741)与 AS 显著相关,复制了先前的结果。这两个 SNP 可能直接或通过其他高连锁不平衡的变体改变转录因子结合位点。
本研究证实了 STX1A 作为 ASC 重要候选基因的作用。STX1A 如何通过确切的分子机制导致病因仍有待阐明。